• Written informed consent and HIPAA authorization for release of personal health information.

‣ NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

⁃ Male or non-pregnant, non-lactating female age ≥ 18 years at the time of consent.

⁃ Karnofsky Performance Status (KPS) of ≥70% within 7 days prior to registration.

⁃ Histological or cytological evidence of pancreatic adenocarcinoma.

⁃ Patients must have resectable primary tumor per NCCN definitions version 2.2021 based on contrast-enhanced CT or MRI (CT or MRI without contrast as part of PET/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis, where resectable is defined as all of the following:

∙ No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery).

‣ No involvement, or \< 180° interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein; and patent portal vein/splenic vein confluence.

‣ No evidence of metastatic disease. NOTE: To minimize ineligible patients, an institutional checklist, identical to the one used by the central radiologist at the end of the study, will be mandated for completion by the enrolling site investigator or radiologist. The 6-point checklist will include visible pancreatic mass; measurable disease; absence of arterial interface; venous interface of less than or equal to 180°; patent portal-splenic confluence; and absence of metastatic disease, including lymphadenopathy outside the surgical basin.

⁃ Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.

⁃ Patients must not have received prior surgery, radiation therapy, chemotherapy, targeted therapy, or any investigational therapy for pancreatic cancer.

⁃ Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.

∙ Hematological

⁃ Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3

• Hemoglobin (Hgb) ≥ 8.0 g/dL

• Platelets ≥100,000/mm3

‣ Renal

• --Calculated creatinine clearance ≥ 30 cc/min using the Cockcroft-Gault formula

‣ Hepatic

⁃ Bilirubin ≤ 1.5 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 3 × ULN

• Alanine aminotransferase (ALT) ≤ 3 × ULN

⁃ Females of childbearing potential must have a negative pregnancy test (serum or urine) within 3 days prior to registration. See the protocol for definition of childbearing potential.

⁃ Females of childbearing potential must be willing to abstain from vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study, and for 6 months after the last dose of study drug(s). Males must be willing to abstain from vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study, and for 3 months after the last dose of study drug(s). See also the protocol (contraception).

⁃ As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

⁃ HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.

⁃ Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.